Proximal 15q variant as possible pitfall in the cytogenetic diagnosis of Prader‐Willi syndrome

Abstract

A patient with Prader‐Willi syndrome showed an elongated proximal 15q, and thus was initially considered to be negative for a proximal 15q deletion. However, repeated high resolution chromosome study demonstrating the DNA‐replication banding patterns revealed an obvious deletion/deficiency of the 15q12 equivalent band on that elongated chromosome 15. This deletion was further verified by comparison with the parental chromosomes 15 and the deleted chromosome 15 was of paternal origin. The elongation was due to a long variant of 15q11.2 band, which has previously been shown to be polymorphic/variable. This variable proximal 15q site could potentially mask a deletion if it is too long, or mimic a deletion if it is too short. The use of the DNA‐replication banding technique instead of the more widely used trypsin banding technique could alleviate this possible pitfall.

Prader–Willi Syndrome, from Molecular Testing and Clinical Study to Diagnostic Protocols

“…Many PWS/AS deletions are not detectable by G-banding. Even at higher band levels, variable G-banding quality, differences in homologue condensation/splitting of band 15q12, and possible presence of extra clinically benign G-bands in this region made interpretation difficult [Hoo et al, 1990;Ludowese et al, 1991). Unreliability of G-banding for deletion detection in the region 15q11-q13 in comparison with FISH has been well documented [Delach et al, 1994;Butler, 1995;Bettio et al, 1995;Smith et al, 1995).…”